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29 March 2024
 
  » pubmed » pmid11099417

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Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters
K E Berge ; H Tian ; G A Graf ; L Yu ; N V Grishin ; J Schultz ; P Kwiterovich ; B Shan ; R Barnes ; H H Hobbs ;
Date 1 Dec 2000
Journal Science, 290 (5497), 1771-5
AbstractIn healthy individuals, acute changes in cholesterol intake produce modest changes in plasma cholesterol levels. A striking exception occurs in sitosterolemia, an autosomal recessive disorder characterized by increased intestinal absorption and decreased biliary excretion of dietary sterols, hypercholesterolemia, and premature coronary atherosclerosis. We identified seven different mutations in two adjacent, oppositely oriented genes that encode new members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter family (six mutations in ABCG8 and one in ABCG5) in nine patients with sitosterolemia. The two genes are expressed at highest levels in liver and intestine and, in mice, cholesterol feeding up-regulates expressions of both genes. These data suggest that ABCG5 and ABCG8 normally cooperate to limit intestinal absorption and to promote biliary excretion of sterols, and that mutated forms of these transporters predispose to sterol accumulation and atherosclerosis.
Source PubMed, pmid11099417 doi: 9022
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